The papers in this themed edition all demonstrate there is still much we do not know about how nutrition can potentially modify critical illness or the gut in children. More is known about adult critical illness and nutritional therapies (1). However, children and not little adults, and the broad age range in pediatrics from term neonates to young adults, along with vastly different pathologies leading to pediatric intensive care unit (PICU) admission represents a challenge to PICU nutrition researchers. This concluding editorial will outline the current state of knowledge in the field and identify what we need to research in the future, based on a recent expert Delphi study (2).
What do we currently know about nutrition in pediatric critical illness?
Several professional societies have recently published their updated guidelines around nutrition in pediatric critical care (3,4) and despite suggesting multiple recommendations, most of these recommendations are based on evidence graded as low. Despite this paucity of well-designed clinical trials in this field, and the drawbacks of circumstantial evidence as we expressed in our editorial introduction, there is observational evidence to show the association between worsened clinical outcomes and nutritional inadequacy. This is both at ICU admission, in malnourished children, and during PICU stay (5), with prolonged mechanical ventilation, more healthcare associated infections (HCAIs), impaired wound healing and delayed sternal closure and increased mortality on children receiving inadequate enteral nutrition (6-10). Randomized trial evidence also showed the potential harm of overfeeding by early parenteral nutrition (PN) in critically ill children (11,12). It appears that throughout the different (and not yet clearly identified) phases of a child’s critical illness, different nutritional targets may be required putting the critically ill child at risk for both under—as well as overfeeding depending on the course of illness. What is apparent is that a ‘one size fits all’ approach will not work, and different subgroups of patients may have different requirements, and these are likely to evolve throughout the course of their critical illness, similar to a pharmacological approach, as discussed in the first editorial.
We also are becoming increasingly aware that predictive energy equations are inadequate for critically ill children (2,13), and although indirect calorimetry (IC) is accurate in some of the PICU population after the acute phase, limitations still exist for the youngest children and those with air leaks (14). Furthermore, energy expenditure is dynamic and determined by multiple intrinsic patient factors and by the PICU therapies applied to the child, yet IC only measures EE at a point in time, and very few (14%) PICUs worldwide have access to a device (15). What we also increasingly know is that many barriers exist to delivering adequate enteral nutrition in the PICU (16), but that many of these are perceived rather than substantiated, lack robust evidence and are applied by risk-averse clinicians (17). Thus, the effective implementation of recommendations and guidance is paramount, with many PICU practices still based on little or no evidence. The routine monitoring of gastric residual volume (GRV) to guide feeding is one such example. This historical practice, lacking any evidence, but used extensively (18,19), almost certainly contributes significantly to time spent without enteral feeds in the PICU and a small study has showed not measuring this did not lead to increased harms (20). This is the challenge for clinicians and researchers now, to implement recent best evidence around nutrition (3,4) into clinical PICU practice and evaluate the effects of this.
What future research is required around nutrition in pediatric critical illness?
In addition to identifying parameters and biomarkers that would allow us to ‘know’ that a child has moved from one phase of critical illness to another, we also do not know the evidence for many of our usual nutritional therapies, different formulas or methods of delivering nutrition. Importantly, unlike adult critical illness (21), we have no valid nutritional risk score for critically ill children, to enable us to predict those at greater risk at the outset and in whom specific nutritional needs and support should be directed to. Uncertainty also persists around the optimal method to determine energy expenditure in many patients such as those on non-invasive respiratory support. Furthermore, we need to know whether a child’s energy expenditure, corresponds directly to their energy requirements. This is the same for protein requirements. The protein balance can be measured, but the optimal target is unknown, and the requirements are almost certain to evolve throughout the course of critical illness. What micronutrient requirements and whether supplementation of specific micronutrient deficits improves outcomes, as does whether pharmaconutrition is beneficial in specific patients and phases of their critical illness.
In addition to understanding the child’s nutritional requirements, then different methods to delivering and achieving nutritional targets need to be better understood. Identification of the optimal methods (gastric versus post-pyloric and continuous versus bolus feeds) and timing for enteral nutrition to in the pediatric critical population is also unknown, and whether certain patients do better with a specific delivery method. Whether one type of enteral nutrition formula (semi-elemental or polymeric) results in better clinical outcomes or improves feed tolerance remains unknown. Indeed, this implies that we have a consistent and reliable definition of feed intolerance and evidence of effective strategies for its management, none of which currently exist. We need to urgently gain international consensus on the definition of ‘feed intolerance’ (22,23). This nebulous concept has been defined differently, thus makes studies difficult to compare and adds to clinician uncertainty (24).
Targeting the improvement of healthcare professionals’ knowledge around nutrition is important, as is the implementation of written protocols and auditing compliance. This ‘implementation science’ must be a fundamental part of future nutrition research, as well as basic and applied science.
We also need to know whether the severe and often rapid muscle breakdown seen in critical illness (25) can be ameliorated by nutrition or additional protein intake or by a combination of nutrition and early rehabilitation interventions. Given the emerging data on the harm of overfeeding in the acute phase of critical illness, we need to know whether targeted permissive underfeeding is beneficial, and if so what level of underfeeding. Finally, a ‘one size fits all’ approach to nutrition in the PICU will not work. Not only does the PICU admit children from term (and sometime preterm) neonates up to young adults, but with vastly different pathologies from sepsis, trauma, congenital heart disease, chronic illness, burns and infectious illnesses. Making assumptions that all these pathological conditions result in the same nutritional demands is misleading and almost certainly incorrect. Yet only a few of these conditions have been studied in some depth: major burns, congenital heart disease, head trauma and bronchiolitis.
In conclusion, although research in this field is rapidly increasing, much of this research is low level evidence and with the biases of being conducted in a single center. Future well conducted clinical trials are urgently needed in many aspects of nutritional care for the critically ill children.
Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/pm-2020-ncc-04). The series “Nutrition in the Critically Ill Child” was commissioned by the editorial office without any funding or sponsorship. LNT, SCATV and FV served as the unpaid Guest Editors of the series. LNT serves as an unpaid editorial board member of Pediatric Medicine from Oct 2019 to Sep 2021. SCATV serves as an unpaid editorial board member of Pediatric Medicine from Oct 2019 to Sep 2021. SCATV reports grants from ESPEN Research Grant, grants from Sophia Research Foundation, grants from Nutricia Research BV, outside the submitted work. FV reports personal fees from BAXTER, personal fees from NUTRICIA, outside the submitted work. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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- Arabi YM, Casaer MP, Chapman M, et al. The intensive care medicine research agenda in nutrition and metabolism. Intensive Care Med 2017;43:1239-56. [Crossref] [PubMed]
- Tume LN, Valla FV, Floh AA, et al. Priorities for nutrition research in pediatric critical care. JPEN J Parenter Enteral Nutr 2019;43:853-62. [Crossref] [PubMed]
- Mehta NM, Skillman HE, Irving SY, et al. Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Pediatr Crit Care Med 2017;18:675-715. [Crossref] [PubMed]
- Tume LN, Valla FV, Joosten K, et al. Nutritional support for children during critical illness: European Society of Pediatric and Neonatal Intensive Care (ESPNIC) metabolism, endocrine and nutrition section position statement and clinical recommendations. Intensive Care Med 2020;46:411-25. [Crossref] [PubMed]
- Valla FV, Baudin F, Gaillard Le Roux B, et al. Nutritional Status Deterioration Occurs Frequently During Children's ICU Stay. Pediatr Crit Care Med 2019;20:714-21. [Crossref] [PubMed]
- Mikhailov TA, Kuhn EM, Manzi J, et al. Early enteral nutrition is associated with lower mortality in critically ill children. JPEN J Parenter Enteral Nutr 2014;38:459-66. [Crossref] [PubMed]
- Srinivasan V, Hasbani NR, Mehta NM, et al. Early enteral nutrition is associated with improved clinical outcomes in critically ill children: a secondary analysis of nutrition support in the heart and lung failure-pediatric insulin titration trial. Pediatr Crit Care Med 2020;21:213-21. [Crossref] [PubMed]
- Larsen BMK, Beggs MR, Leong AY, et al. Can energy intake alter clinical and hospital outcomes in PICU? Clin Nutr ESPEN 2018;24:41-6. [Crossref] [PubMed]
- Larsen BM, Goonewardene LA, Field CJ, et al. Low energy intakes are associated with adverse outcomes in infants after open heart surgery. JPEN J Parenter Enteral Nutr 2013;37:254-60. [Crossref] [PubMed]
- Mehta NM, Bechard LJ, Cahill N, et al. Nutritional practices and their relationship to clinical outcomes in critically ill children--an international multicenter cohort study*. Crit Care Med 2012;40:2204-11. [Crossref] [PubMed]
- Fivez T, Kerklaan D, Mesotten D, et al. Early versus late parenteral nutrition in critically ill children. N Engl J Med 2016;374:1111-22. [Crossref] [PubMed]
- Jotterand Chaparro C, Taffé P, Moullet C, et al. Performance of predictive equations specifically developed to estimate resting energy expenditure in ventilated critically ill children. J Pediatr 2017;184:220-6.e5. [Crossref] [PubMed]
- Delsoglio M, Achamrah N, Berger MM, et al. Indirect calorimetry in clinical practice. J Clin Med 2019;8:1387. [Crossref] [PubMed]
- Kerklaan D, Fivez T, Mehta NM, et al. Worldwide survey of nutritional practices in PICUs. Pediatr Crit Care Med 2016;17:10-8. [Crossref] [PubMed]
- Tume LN, Eveleens RD, Verbruggen SCAT, et al. Barriers to delivery of enteral nutrition in pediatric intensive care: a world survey. Pediatr Crit Care Med 2020. [Epub ahead of print]. [Crossref] [PubMed]
- Tume LN, Balmaks R, da Cruz E, et al. Enteral Feeding practices in infants with congenital heart disease across European PICUs: a European Society of pediatric and neonatal intensive care survey. Pediatr Crit Care Med 2018;19:137-44. [Crossref] [PubMed]
- Tume LN, Woolfall K, Arch B, et al. Routine gastric residual volume measurement to guide enteral feeding in mechanically ventilated infants and children: the GASTRIC feasibility study. Health Technol Assess 2020;24:1-120. [Crossref] [PubMed]
- Tume LN, Latten L, Kenworthy L. Paediatric intensive care nurses' decision-making around gastric residual volume measurement. Nurs Crit Care 2017;22:293-7. [Crossref] [PubMed]
- Tume LN, Bickerdike A, Latten L, et al. Routine gastric residual volume measurement and energy target achievement in the PICU: a comparison study. Eur J Pediatr 2017;176:1637-44. [Crossref] [PubMed]
- de Vries MC, Koekkoek WK, Opdam MH, et al. Nutritional assessment of critically ill patients: validation of the modified NUTRIC score. Eur J Clin Nutr 2018;72:428-35. [Crossref] [PubMed]
- Johnson RW, Ng KWP, Dietz AR, et al. Muscle atrophy in mechanically-ventilated critically ill children. PLoS One 2018;13:e0207720. [Crossref] [PubMed]
- Valla FV, Young DK, Rabilloud M, et al. Thigh ultrasound monitoring identifies decreases in quadriceps femoris thickness as a frequent observation in critically ill children. Pediatr Crit Care Med 2017;18:e339-47. [Crossref] [PubMed]
- Tume LN, Valla FV. A review of feeding intolerance in critically ill children. Eur J Pediatr 2018;177:1675-83. [Crossref] [PubMed]
- Eveleens RD, Joosten KFM, de Koning BAE, et al. Definitions, predictors and outcomes of feeding intolerance in critically ill children: a systematic review. Clin Nutr 2020;39:685-93. [Crossref] [PubMed]
- Gadhvi KR, Valla FV, Tume LN. Review of outcomes used in nutrition trials in pediatric critical care. JPEN J Parenter Enteral Nutr 2020. [Epub ahead of print]. [Crossref] [PubMed]
Cite this article as: Tume LN, Verbruggen SCAT, Valla F. The current state of knowledge and research required around nutrition in pediatric critical illness. Pediatr Med 2020;3:7.